Therapy control based on cardiopulmonary status

ABSTRACT

Methods and systems provide an approach to therapy control based on assessment of a patient&#39;s cardiopulmonary status. Conditions sensed via sensors of an external respiratory therapy device are used to assess a patient&#39;s cardiopulmonary status. The respiratory therapy device sensors may be utilized alone or in combination with other sensors to determine cardiopulmonary status of a patient. Therapy delivered to the patient is controlled based on the cardiopulmonary status assessment. For example, therapy delivered to the patient may be initiated, terminated, and/or modified based on the assessed cardiopulmonary status of the patient. Cardiopulmonary status assessment, therapy control, or both, are performed by an implantable device.

RELATED PATENT DOCUMENTS

This application is a continuation of U.S. patent application Ser. No.10/930,346, filed on Aug. 31, 2004, now U.S. Pat. No. 7,662,101, whichclaims the benefit of Provisional Patent Application Ser. No. 60/504,477and 60/504,723, both filed on Sep. 18, 2003, to which Applicant claimspriority under 35 U.S.C. §120 and 35 U.S.C. §119(e), respectively, andwhich are incorporated herein by reference in their entireties.

FIELD OF THE INVENTION

The present invention relates generally to controlling therapy based onthe cardiopulmonary status of a patient.

BACKGROUND OF THE INVENTION

The human body functions through a number of interdependentphysiological systems controlled through various mechanical, electrical,and chemical processes. The metabolic state of the body is constantlychanging. For example, as exercise level increases, the body consumesmore oxygen and gives off more carbon dioxide. The cardiac and pulmonarysystems maintain appropriate blood gas levels by making adjustments thatbring more oxygen into the system and dispel more carbon dioxide. Thecardiovascular system transports blood gases to and from the bodytissues. The respiration system, through the breathing mechanism,performs the function of exchanging these gases with the externalenvironment. Together, the cardiac and respiration systems form a largeranatomical and functional unit denoted the cardiopulmonary system.

Various disorders may affect the cardiovascular, respiratory, and otherphysiological systems. Diseases and disorders of the cardiac andpulmonary systems, are among the leading causes of acute and chronicillness in the world. For example, heart failure (HF) is a clinicalsyndrome that impacts a number of physiological processes, includingrespiration. Heart failure is an abnormality of cardiac function thatcauses cardiac output to fall below a level adequate to meet themetabolic demand of peripheral tissues. Heart failure is usuallyreferred to as congestive heart failure (CHF) due to the accompanyingvenous and pulmonary congestion. Congestive heart failure may have avariety of underlying causes, including ischemic heart disease (coronaryartery disease), hypertension (high blood pressure), and diabetes, amongothers. Other cardiac disorders include cardiac rhythm disorders, suchas bradycardia (a heart rhythm that is too slow) and tachyarrhythmia (aheart rhythm that is too fast).

Pulmonary diseases or disorders may be organized into variouscategories, including, for example, breathing rhythm disorders,obstructive diseases, restrictive diseases, infectious diseases,pulmonary vasculature disorders, pleural cavity disorders, and others.Symptoms of pulmonary dysfunction may include symptoms such as apnea,dyspnea, changes in blood or respiratory gases, symptomatic respiratorysounds, e.g., coughing, wheezing, and general degradation of pulmonaryfunction, among other symptoms.

Breathing rhythm disorders involve patterns of interrupted and/ordisrupted breathing. Sleep apnea syndrome (SAS) and Cheyne-Stokesrespiration (CSR) are examples of breathing rhythm disorders. Breathingrhythm disorders may be caused by an obstructed airway or by derangementof the signals from the brain controlling respiration. Sleep disorderedbreathing is particularly prevalent and is associated with excessivedaytime sleepiness, systemic hypertension, increased risk of stroke,angina, and myocardial infarction. Breathing rhythm disorders can beparticularly serious for patients concurrently suffering fromcardiovascular deficiencies.

Obstructive pulmonary diseases may be associated with a decrease in thetotal volume of exhaled air flow caused by a narrowing or blockage ofthe airways. Examples of obstructive pulmonary diseases include asthma,emphysema and bronchitis. Chronic obstructive pulmonary disease (COPD)refers to chronic lung diseases that result in blocked air flow in thelungs. Chronic obstructive pulmonary disease generally develops overmany years, typically from exposure to cigarette smoke, pollution, orother irritants. Over time, the elasticity of the lung tissue is lost,the lung's air sacs may collapse, the lungs may become distended,partially clogged with mucus, and lose the ability to expand andcontract normally. As the disease progresses, breathing becomes labored,and the patient grows progressively weaker. Many people with COPDconcurrently have both emphysema and chronic bronchitis.

Restrictive pulmonary diseases involve a decrease in the total volume ofair that the lungs are able to hold. Often the decrease in total lungvolume is due to a decrease in the elasticity of the lungs themselves,or may be caused by a limitation in the expansion of the chest wallduring inhalation. Restrictive pulmonary disease may be the result ofscarring from pneumonia, tuberculosis, or sarcoidosis. A decrease inlung volume may be caused by various neurological and muscular diseasesaffecting the neural signals and/or muscular strength of the chest walland lungs. Examples of neurological and/or muscular diseases that mayaffect lung volume include poliomyelitis and multiple sclerosis. Lungvolume deficiencies may also be related to congenital or acquireddeformities of the chest.

Pulmonary dysfunctions may also involve disorders of the pleural cavityand/or pulmonary vasculature. Pulmonary vasculature disorders mayinclude pulmonary hypertension, pulmonary edema, and pulmonary embolism.Disorders of the pleural cavity include conditions such as pleuraleffusion, pneumothorax, and hemothorax, for example.

Pulmonary diseases may be caused by infectious agents such as viraland/or bacterial agents. Examples of infectious pulmonary diseasesinclude pneumonia, tuberculosis, and bronchiectasis. Othernon-infectious pulmonary diseases include lung cancer and adultrespiratory distress syndrome (ARDS), for example.

Therapy may be more effectively delivered to a patient to alleviate thediseases and disorders discussed above if the patient's cardiopulmonarystatus is known. Methods and systems for controlling therapy based oncardiopulmonary status are desirable.

SUMMARY OF THE INVENTION

Various embodiments of present invention involve methods and systems forcontrolling therapy based on the cardiopulmonary status of the patient.One embodiment of the invention involves a method for controlling atherapy delivered to a patient based on cardiopulmonary status. One ormore physiological conditions are sensed using an external respiratorytherapy device. The patient's cardiopulmonary status is assessed basedon the sensed physiological conditions. Therapy delivered to the patientis controlled based on the patient's cardiopulmonary status. At leastone of assessing the patient's cardiopulmonary status and controllingthe therapy is performed at least in part implantably.

According to various aspects of the invention, the physiologicalconditions are sensed using the sensors of a disordered breathingtherapy device. The sensed physiological conditions may include, forexample, sensing respiratory pressure, flow, and/or exhaled gasconcentration.

In accordance with another aspect of the invention, the sensor system ofan additional medical device, different from the respiratory therapydevice may be used to sense additional physiological conditions used toassess cardiopulmonary status. In one implementation, the additionalmedical device comprises an implantable cardiac therapy device.

In accordance with another embodiment of the invention, a medicaltherapy control system controls therapy based on a patient'scardiopulmonary status. The control system includes an externalrespiratory device including a sensor system configured to sense one ormore physiological conditions. A cardiopulmonary status processor iscoupled to the sensor system. The cardiopulmonary status processor isconfigured to determine a cardiopulmonary status of a patient based onthe sensed physiological conditions. A therapy controller is configuredto control a therapy delivered to the patient based on the patient'scardiopulmonary status. At least one of the cardiopulmonary statusprocessor and the therapy controller include an implantable component.

The above summary of the present invention is not intended to describeeach embodiment or every implementation of the present invention.Advantages and attainments, together with a more complete understandingof the invention, will become apparent and appreciated by referring tothe following detailed description and claims taken in conjunction withthe accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a flowchart illustrating a method of determining a presenceof a non-rhythm pulmonary disease and delivering therapy in accordancewith embodiments of the invention;

FIGS. 1B-1D are graphs of normal, obstructive and restrictiverespiratory patterns, respectively, in accordance with embodiments ofthe invention;

FIGS. 1E and 1F are block diagrams of medical systems that may be usedto implement therapy control based on cardiopulmonary status assessmentin accordance with embodiments of the invention;

FIG. 2 illustrates a medical system including an external respiratorydevice and an implantable device that may be used to assess thepatient's cardiopulmonary status and control the delivery of therapy inaccordance with embodiments of the invention;

FIG. 3 illustrates a medical system including an external respiratorydevice and a cardiac rhythm management device that may be used to assessthe patient's cardiopulmonary status and control the delivery of therapyin accordance with embodiments of the invention;

FIGS. 4 and 5 are partial views of implantable cardiac devices that maybe used for cardiopulmonary status assessment and therapy control inaccordance with embodiments of the invention;

FIGS. 6A-6N illustrate a chart depicting relationships between pulmonarydiseases, symptoms and/or physiological changes caused by the pulmonarydiseases, and conditions used to detect the symptoms and/orphysiological changes that may be used to assess cardiopulmonary statusand/or detect a presence of cardiopulmonary disease in accordance withembodiments of the invention; and

FIG. 7 is a flowchart illustrating a method of assessing a presence of anon-rhythm pulmonary disease and delivering drug therapy in accordancewith embodiments of the invention.

While the invention is amenable to various modifications and alternativeforms, specifics thereof have been shown by way of example in thedrawings and will be described in detail below. It is to be understood,however, that the intention is not to limit the invention to theparticular embodiments described. On the contrary, the invention isintended to cover all modifications, equivalents, and alternativesfalling within the scope of the invention as defined by the appendedclaims.

DETAILED DESCRIPTION OF VARIOUS EMBODIMENTS

In the following description of the illustrated embodiments, referencesare made to the accompanying drawings which form a part hereof, and inwhich are shown by way of illustration, various embodiments by which theinvention may be practiced. It is to be understood that otherembodiments may be utilized, and structural and functional changes maybe made without departing from the scope of the present invention.

Pulmonary disorders may be organized into broad categories encompassingdisorders related to breathing rhythm and non-rhythm related pulmonarydiseases and/or disorders. Breathing rhythm disorders include varioussyndromes characterized by patterns of disordered breathing that produceinsufficient respiration, for example, sleep apnea, hypopnea, andCheyne-Stokes Respiration (CSR), among others. Breathing rhythmdisorders are not necessarily accompanied by alteration of pulmonarystructures.

Non-rhythm pulmonary diseases or disorders typically involve physicalchanges to lung structures, such as loss of elasticity of the lungtissue, obstruction of airways with mucus, limitation of the expansionof the chest wall during inhalation, fibrous tissue within the lung,excessive pressure in the pulmonary arteries, and/or othercharacteristics. Pulmonary diseases or disorders that are notrhythm-related are referred to herein as non-rhythm pulmonary diseases.Non-rhythm related pulmonary diseases/disorders may include obstructivepulmonary diseases, restrictive pulmonary diseases, infectious andnon-infectious pulmonary diseases, pulmonary vasculature disorders, andpleural cavity disorders, for example.

Embodiments of the invention involve methods of controlling a therapydelivered to the patient, as illustrated in the flowchart of FIG. 1A.One or more physiological conditions are sensed 102 using the sensingsystem of an external respiratory therapy device. In variousimplementations, the external respiratory therapy device may comprise,for example, a gas therapy device, nebulizer, ventilator, positiveairway pressure device, or other type of respiration therapy device. Thepatient's cardiopulmonary status is assessed 104 based on the sensedphysiological conditions. Therapy delivered to the patient is controlled106 based on the patient's cardiopulmonary status. The therapy may beused to treat breathing rhythm disorders, non-rhythm related pulmonarydiseases/disorders, cardiac disorders, and/or other diseases ordisorders affecting the patient.

In one embodiment, an implantable device may be used to sense 103additional physiological conditions. The patient's cardiopulmonarystatus is assessed 104 based on the physiological conditions sensed bythe external respiratory device and the additional physiologicalconditions sensed by the implantable device. At least one of assessingthe patient's cardiopulmonary status and controlling the therapy isperformed at least in part implantably. Implantably performing anoperation comprises performing the operation using a component, device,or system that is partially or fully implanted within the body.

In one implementation, the presence of a cardiac and/or pulmonarydisease or disorder is detected and therapy to treat the disease ordisorder is delivered to the patient. The therapy may be modified toimprove therapy effectiveness based on the assessment of the cardiacand/or pulmonary disease or disorder. In another embodiment of theinvention, the patient's cardiopulmonary status is assessed and thetherapy delivered to the patient is modified to enhance patient comfortor to achieve another result.

For example, the patient's cardiopulmonary status may be assessed basedon sensed physiological conditions indicative of symptoms orphysiological changes associated with a particular disease or disorder.A respiratory therapy device used to sense the physiological conditionsmay comprise, for example, a gas therapy device, nebulizer, ventilator,positive airway pressure device, or other type of respiration therapydevice. In a preferred embodiment, the respiratory therapy devicecomprises a positive airway pressure device. Continuous positive airwaypressure (CPAP) devices are frequently used to treat sleep apnea and/orother breathing rhythm disorders. A CPAP device may be used regularlyduring a patient's sleep time to prevent or treat sleep disorderedbreathing events. Use of a CPAP device for treatment of breathing rhythmdisorders facilitates detection of rhythm-related and non-rhythm relatedpulmonary diseases. The CPAP device provides sensors available on aperiodic basis, e.g., nightly, that may be used to sense conditionsindicative of cardiopulmonary status.

In another implementation, assessment of the cardiopulmonary status ofthe patient is based on one or more physiological conditions sensedusing a patient-external respiratory therapy device and on one or moreadditional physiological conditions sensed using a cardiac device. Thecardiac device may comprise, for example, an implantable cardiac therapydevice, such as a pacemaker, defibrillator, cardioverter, cardiacmonitor, and/or cardiac resynchronizer.

In yet another implementation, assessment of the cardiopulmonary statusof the patient is based on one or more physiological conditions sensedusing a patient-external respiratory therapy device and one or moreadditional conditions sensed or detected using an additionalpatient-external device. The patient-external device may comprise, forexample, a patient operated input device, a patient informationdatabase, or a network-connected server, for example.

According to one aspect of the invention, pulmonary function testing maybe employed to detect physiological changes associated with the presenceof cardiac and/or pulmonary disease. Pulmonary function tests may beused to evaluate lung mechanics, gas exchange, pulmonary blood flow, andblood gases and pH. They are used to evaluate patients in the diagnosisof pulmonary disease, assessment of disease development, or evaluationof the risk of pulmonary complications from surgery.

Pulmonary function testing is conventionally performed in a clinicalsetting and measures values indicative of the ability of the lungs toexchange oxygen and carbon dioxide. The total lung capacity (TLC) isdivided into four volumes. The tidal volume (V_(T)) is the volumeinhaled or exhaled in normal quiet breathing. The inspiratory reservevolume (IRV) is the maximum volume that can be inhaled following anormal quiet inhalation. The expiratory reserve volume (ERV) is themaximum volume that can be exhaled following a normal quiet exhalation.The residual volume (RV) is the volume remaining in the lungs followinga maximal exhalation. The vital capacity (VC) is the maximum volume thatcan be exhaled following a maximal inhalation; VC=IRV+V_(T)+ERV. Theinspiratory capacity (IC) is the maximum volume that can be inhaledfollowing a normal quiet exhalation; IC=IRV+V_(T). The functionalresidual capacity (FRC) is the volume remaining in the lungs following anormal quiet exhalation; FRC=ERV+RV.

The vital capacity and its components (V_(T), IRV, ERV, IC) aretypically measured using a spirometer, which is a device that measuresthe volumes of air inhaled and exhaled. The FRC is usually measured bythe helium dilution method using a closed spirometry system. A knownamount of helium is introduced into the system at the end of a normalquiet exhalation. When the helium equilibrates throughout the volume ofthe system, which is equal to the FRC plus the volume of the spirometerand tubing, the FRC is determined from the helium concentration. Thistest may underestimate the FRC of patients with emphysema. The FRC canbe determined quickly and more accurately by body plethysmography. Theresidual volume and total lung capacity are determined from the FRC.

In the forced vital capacity (FVC) maneuver, the patient exhales asforcefully and rapidly as possible, beginning at maximal exhalation.Several parameters are determined from the spirogram. The FVC is thetotal volume of air exhaled during the maneuver; it is normally equal tothe vital capacity. The forced expiratory volume (FEV) is the volumeexpired during a specified time period from the beginning of the test.The times used are 0.5, 1, 2, and 3 seconds; corresponding parametersare FEW)_(0.5), FEV_(1.0), FEV_(2.0), and FEV_(3.0). The maximalexpiratory flow rate (MEFR) is the slope of the line connecting thepoints where 200 ml and 1200 ml have been exhaled; it is also calledFEF₂₀₀₋₁₂₀₀ (forced expiratory flow). The maximal midexpiratory flowrate (MMFR, MMF) is the slope of the line connecting the points where 25percent and 75 percent of the FVC have been exhaled; it is also calledFEF_(25-75%).

The Maximal Voluntary Ventilation (MVV) is the maximal volume of airthat can be breathed by the patient, expressed in liters per minute; itwas formerly called maximal breathing capacity (MBC). The patientbreathes as rapidly and deeply as possible for 12 to 15 seconds and thevolume exhaled is determined by spirometry.

Various parameters related to pulmonary performance, some of which maybe measured using sensors of a respiratory therapy device include, forexample, tidal volume, minute ventilation, inspiratory reserve volume,forced expiratory volume, residual volume, and forced vital capacity,among other parameters. According to one embodiment, testing of somepulmonary function parameters may be performed using the ventilationpressure and ventilation flow sensors of a CPAP device or otherpatient-external respiratory therapy device. The pulmonary functiontesting may be used, for example, to assess a presence of restrictiveand/or obstructive pulmonary disorders as indicated in FIGS. 1B-1D.

Pulmonary performance may be evaluated based on data acquired by therespiratory therapy device during normal and forced inspiration andexpiration. From such data, pulmonary parameters including tidal volume,minute ventilation, forced expiratory volume, forced vital capacity,among other parameters may be determined.

Because the results of pulmonary function tests vary with size and age,the normal values are calculated using prediction equations ornomograms, which give the normal value for a specific age, height, andsex. The prediction equations are derived using linear regression on thedata from a population of normal subjects. The observed values areusually reported as a percentage of the predicted value. Abnormal testresults may show either an obstructive or restrictive pattern.Sometimes, both patterns are present.

FIG. 1B illustrates a normal respiratory pattern, having normal FEV andFVC. FIG. 1C illustrates an obstructive pattern. An obstructive patternoccurs when there is airway obstruction from any cause, as in asthma,bronchitis, emphysema, or advanced bronchiectasis; these conditions aregrouped together in the nonspecific term chronic obstructive pulmonarydisease (COPD). In this pattern, the residual volume is increased andthe RV/TLC ratio is markedly increased. Owing to increased airwayresistance, the flow rates are decreased. The FEV/FVC ratios, MMFR, andMEFR are all decreased; FEV_(1.0)/FVC is less than 75 percent.

FIG. 1D illustrates a restrictive pattern. A restrictive pattern occurswhen there is a loss of lung tissue or when lung expansion is limited asa result of decreased compliance of the lung or thorax or of muscularweakness. The conditions in which this pattern can occur include pectusexcavatum, myasthenia gravis, diffuse idiopathic interstitial fibrosis,and space occupying lesions (tumors, effusions). In this pattern, thevital capacity and FVC are less than 80 percent of the predicted value,but the FEV/FVC ratios are normal. The TLC is decreased and the RV/TLCratio is normal.

Embodiments of the invention utilize a patient-external respiratorytherapy device to perform periodic pulmonary function testing. A CPAP orother external respiratory device may measure ventalitory pressure,ventilatory airflow, and/or ventalitory gas concentration duringperiodic, e.g., nightly, therapy sessions. The ventalitory pressureand/or airflow measurements may be used to measure FVC and FEV duringforced expiration. From these two parameters, FEV/FVC can be derived todifferentiate obstructive versus restrictive respiratory patterns asshown in the FIGS. 1C and 1D. Other measurements that are possible usingthe respiratory device sensors include low forced expiratory flow (FEF),high functional residual capacity (FRC), total lung capacity (TLC), andhigh residual volume (RV).

In one embodiment, the patient may perform forced expirations whileconnected to the external respiratory device. During the forcedexpirations, circuitry in the external respiratory device may collectmeasurements, including measurements useful in calculating the FEV andFVC measurements.

In addition, the forced expiratory flow (FEF_(25-75%)) may be measured.The middle half by volume of the total expiration is marked, and itsduration is measured. The FEF_(25-75%) is the volume in liters dividedby the time in seconds. In patients with obstructive diseases, theFEF_(25-75%) is generally greater than their expected values.

Circuitry incorporated in the CPAP device may be used to comparemeasured FVC, FEV and FEF_(25-75%) values derived from the respiratorytherapy device pressure sensors and/or airflow sensors with predictedvalues from normal subjects in accordance with various embodiments. Thecomparison provides diagnostic information of lung mechanics. Dataacquired by the CPAP device may be transmitted, for example, from therespiratory therapy device to an advanced patient management (APM)system or other remote device.

The results of pulmonary function testing, along with otherphysiological conditions measured by the CPAP and/or other devices ofthe system, may be compared to initial or baseline results to detectchanges and/or determine trends in the patient's cardiopulmonary statusover time. The changes from baseline values may be used to discern apresence of disease processes. Further, over time, a database ofinformation about relevant conditions and specific to the patient isestablished. The information may be used to develop sets of criteriaspecific to the patient and associated with the presence of a particularcardiac and/or pulmonary disease processes. Thus, in someimplementations, the system may learn to recognize the presence ofdisease based on the history of symptoms and/or physiological changesthat occur in a particular patient.

In some embodiments, pulmonary function testing may be performed using acardiac rhythm management system (CRM) or other implantable device. Inone implementation, the pulmonary function testing is performed using animplanted transthoracic impedance sensor. Transthoracic impedancesensing has been used in connection with rate-adaptive pacemakers tomeasure respiration cycles. An impedance sensor may be used to measurethe variation in transthoracic impedance, which increases during theinspiratory and decreases during the expiratory phase of a respirationcycle. The sensor injects a sub-threshold stimulating current betweenthe pacemaker case and an electrode on an intracardiac or subcutaneouslead, and measures the voltage across the case and another electrode onthe same or another lead. Clinical investigations have shown that theimpedance sensor can measure respiratory rate tidal volume, and minuteventilation accurately.

In accordance with various embodiments of the invention, a properlycalibrated impedance sensor, implemented in cooperation with a pacemakeror other implantable device, may be used to measure FVC and FEV duringforced expiration. From these two parameters, FEV/FVC can be derived todifferentiate obstructive versus restrictive respiratory patterns asshown in the FIGS. 1C and 1D, respectively.

In addition, the forced expiratory flow (FEF_(25-75%)) may be measured.The middle half by volume of the total expiration is marked, and itsduration is measured. The FEF_(25-75%) is the volume in liters dividedby the time in seconds. In patients with obstructive diseases, theFEF_(25-75%) is generally greater than their expected values.

The implantable device may be used to compare measured FVC, FEV andFEF_(25-75%) values derived from the implanted impedance sensor withpredicted values from normal subjects in accordance with variousembodiments. The comparison provides diagnostic information of lungmechanics.

Data acquired using the above-described techniques may be transmittedfrom the implantable device to an advanced patient management system orother remote device. Assessment of the patient's cardiopulmonary statusor control of the therapy may be performed by the advanced patientmanagement system.

Methods and systems for acquiring and using pulmonary function testinginformation, aspects of which may be utilized in connection withembodiments of the invention, are described in commonly owned U.S. Pat.No. 7,329,226, which is incorporated herein by reference.

FIGS. 1E and 1F are block diagrams of medical systems that may be usedto implement therapy control based on cardiopulmonary status assessmentin accordance with embodiments of the invention. In these embodiments,the system utilizes a sensor system 110 of a respiratory therapy device120 to sense one or more physiological conditions. For example, thesensor system 110 may sense conditions associated with patientrespiration, including breathing cycles, respiratory pressure,concentration of respiratory gases, respiratory airflow, and/or otherphysiological conditions. The respiratory therapy device 110 includes arespiratory therapy delivery system 115, such as a positive airwaypressure delivery system in the case of a CPAP device, for example.

The system includes a cardiopulmonary status processor 130 coupled tothe respiratory therapy sensor system 110. The cardiopulmonary statusprocessor assesses the patient's cardiopulmonary status. Assessment ofcardiopulmonary status may include evaluating the patient's pulmonaryfunction as previously described. In some implementations, thecardiopulmonary status processor may work in cooperation with therespiratory therapy device, and/or other therapy or diagnostic devicesto perform the pulmonary function testing required or desired.Cardiopulmonary status evaluation may comprise determining and/orassessing a presence of cardiac and/or pulmonary disease. The chartsprovided in FIGS. 6A-6N illustrate conditions and sensors that may beused to sense physiological changes associated with various cardiacand/or pulmonary diseases and disorders.

As illustrated in FIG. 1E, the system include a therapy controller 140,that develops control signals that may be used to control one or moretherapy devices 160.

FIG. 1F illustrates another embodiment of the invention. The embodimentillustrated in FIG. 1F includes a cardiac therapy device 150 including acardiac therapy sensor system 154 that is used in combination with therespiratory therapy sensor system 110 to assess the patient'scardiopulmonary status. Signals from the cardiac therapy sensor system154 and the respiratory therapy system 115 are utilized by thecardiopulmonary status processor 130 to determine the cardiopulmonarystatus of the patient. Assessment of the patient's cardiopulmonarystatus may involve sensing a presence of a cardiac and/or pulmonarydisease. The sensor systems 110, 154, of one or both of the respiratorytherapy device 120, the cardiac therapy device 154, and/or other sensorsystems (not shown), may be used for cardiopulmonary status assessment.

The sensor systems 110, 154, may be used in connection with performingpulmonary function testing as described above. Cardiopulmonary statusassessment may comprise determining and/or assessing a presence ofcardiac and/or pulmonary disease. The charts provided in FIGS. 6A-6Nillustrate conditions and sensors that may be used to sensephysiological changes associated with various cardiac and/or pulmonarydiseases and disorders. According to one aspect of the invention, thecardiopulmonary status processor may assess a presence of a cardiacdisease/disorder. The cardiac disease/disorder assessment may involve,for example, cardiac rhythm related disorders, arterial diseases, heartfailure, and/or hypertension.

The cardiopulmonary status processor may be used to detect a presence ofone or more rhythm-related and/or non-rhythm related pulmonarydiseases/disorders. Rhythm-related breathing disorders involvedisruption of the normal respiratory cycle. Although disorderedbreathing often occurs during sleep, the condition may also occur whilethe patient is awake.

Breathing rhythm disorders may include, for example, apnea, hypopnea,Cheyne-Stokes respiration, periodic breathing, as indicated in thecharts of FIGS. 6A-6N, and/or other disorders manifested by disruptionof normal breathing cycles. Apnea is a fairly common disordercharacterized by periods of interrupted breathing. Apnea is typicallyclassified based on its etiology. One type of apnea, denoted obstructiveapnea, occurs when the patient's airway is obstructed by the collapse ofsoft tissue in the rear of the throat. Central apnea is caused by aderangement of the central nervous system control of respiration. Thepatient ceases to breathe when control signals from the brain to therespiratory muscles are absent or interrupted. Mixed apnea is acombination of the central and obstructive apnea types. Regardless ofthe type of apnea, people experiencing an apnea event stop breathing fora period of time. The cessation of breathing may occur repeatedly duringsleep, sometimes hundreds of times a night and sometimes for a minute orlonger.

In addition to apnea, other types of disordered respiration cycles havebeen identified, including hypopnea (shallow breathing), tachypnea(rapid breathing), hyperpnea (heavy breathing), and dyspnea (laboredbreathing). Combinations of the respiratory cycles described above maybe observed, including, for example, periodic breathing andCheyne-Stokes respiration (CSR). Periodic breathing is characterized bycyclic respiratory patterns that may exhibit rhythmic rises and falls intidal volume. Cheyne-Stokes respiration is a specific form of periodicbreathing wherein the tidal volume decreases to zero resulting in apneicintervals. The breathing interruptions of periodic breathing and CSR maybe associated with central apnea, or may be obstructive in nature. CSRis frequently observed in patients with congestive heart failure (CHF)and is associated with an increased risk of accelerated CHF progression.Because of the cardiopulmonary implications, detection and therapy fordisordered breathing is of particular interest.

Disordered breathing may be detected by sensing and analyzing variousconditions associated with disordered breathing. Table 1 providesexamples of how a representative subset of physiological andnon-physiological, contextual conditions may be used in connection withdisordered breathing detection.

TABLE 1 Examples of how condition may be used in Condition TypeCondition disordered breathing detection Physiological Heart rateDecrease in heart rate may indicate disordered breathing episode.Increase in heart rate may indicate autonomic arousal from a disorderedbreathing episode. Decrease in heart rate may indicate the patient isasleep. Heart rate Disordered breathing causes heart rate variabilityvariability to decrease. Changes in HRV associated with sleep disorderedbreathing may be observed while the patient is awake or asleepVentricular filling May be used to identify/predict pulmonary pressurecongestion associated with respiratory disturbance. Blood pressureSwings in on-line blood pressure measures are associated with apnea.Disordered breathing generally increases blood pressure variability -these changes may be observed while the patient is awake or asleep.Snoring Snoring is associated with a higher incidence of obstructivesleep apnea and may be used to detect disordered breathing. RespirationRespiration patterns including, e.g., respiration pattern/rate rate, maybe used to detect disordered breathing episodes. Respiration patternsmay be used to determine the type of disordered breathing. Respirationpatterns may be used to detect that the patient is asleep. Patency ofupper Patency of upper airway is related to airway obstructive sleepapnea and may be used to detect episodes of obstructive sleep apnea.Pulmonary Pulmonary congestion is associated with congestion respiratorydisturbances. Sympathetic End of apnea associated with a spike in SNA.nerve activity Changes in SNA observed while the patient is awake orasleep may be associated with sleep disordered breathing CO2 Low CO2levels initiate central apnea. O2 O2 desaturation occurs during severeapnea/hypopnea episodes. Blood alcohol Alcohol tends to increaseincidence of snoring content & obstructive apnea. Adrenalin End of apneaassociated with a spike in blood adrenaline. BNP A marker of heartfailure status, which is associated with Cheyne-Stokes RespirationC-Reactive A measure of inflammation that may be related Protein toapnea. Drug/Medication/ These substances may affect the incidence ofTobacco use both central & obstructive apnea. Muscle atonia Muscleatonia may be used to detect REM and non-REM sleep. Eye movement Eyemovement may be used to detect REM and non-REM sleep. Non- TemperatureAmbient temperature may be a condition physiological predisposing thepatient to episodes of disordered breathing and may be useful indisordered breathing detection. Humidity Humidity may be a conditionpredisposing the patient to episodes of disordered breathing and may beuseful in disordered breathing detection. Pollution Pollution may be acondition predisposing the patient to episodes of disordered breathingand may be useful in disordered breathing detection. Posture Posture maybe used to confirm or determine the patient is asleep. Activity Patientactivity may be used in relation to sleep detection. Location Patientlocation may used to determine if the patient is in bed as a part ofsleep detection. Altitude Lower oxygen concentrations at higheraltitudes tends to cause more central apnea

In one embodiment, episodes of disordered breathing may be detected bymonitoring the respiratory waveform output of a transthoracic impedancesensor. When the tidal volume (TV) of the patient's respiration, asindicated by the transthoracic impedance signal, falls below a hypopneathreshold, then a hypopnea event is declared. For example, a hypopneaevent may be declared if the patient's tidal volume falls below about50% of a recent average tidal volume or other baseline tidal volumevalue. If the patient's tidal volume falls further to an apneathreshold, e.g., about 10% of the recent average tidal volume or otherbaseline value, an apnea event is declared.

In various embodiments, episodes of disordered breathing may be detectedby analyzing the patient's respiratory cycles. For example, thepatient's respiration cycles may be detected using a transthoracicimpedance sensor, external respiratory bands, or other sensor configuredto sense a signal modulated by patient respiration. A respiration cyclemay be divided into an inspiration period corresponding to the patientinhaling, an expiration period, corresponding to the patient exhaling,and a non-breathing period occurring between inhaling and exhaling.Respiration intervals are established using inspiration and expirationthresholds. The inspiration threshold marks the beginning of aninspiration period and may be determined by the sensor signal risingabove the inspiration threshold. The respiration cycle may be determinedto transition from an inspiration period to an expiration period whenthe sensor signal is maximum. The expiration interval continues untilthe sensor signal falls below an expiration threshold. A non-breathinginterval starts from the end of the expiration period and continuesuntil the beginning of the next inspiration period.

Detection of apnea and severe apnea according to embodiments of theinvention may be accomplished based on the length of the patient'snon-breathing periods. A condition of apnea is detected when anon-breathing period exceeds a first predetermined interval, denoted theapnea interval. A condition of severe apnea is detected when thenon-breathing period exceeds a second predetermined interval, denotedthe severe apnea interval. For example, apnea may be detected when thenon-breathing interval exceeds about 10 seconds, and severe apnea may bedetected when the non-breathing interval exceeds about 20 seconds.Methods and systems for detecting breathing rhythm disorders, aspects ofwhich may be utilized in connection with a therapy control systemdescribed herein, are described in commonly owned U.S. Pat. No.7,252,640, which is incorporated herein by reference.

Detection of apnea and severe apnea may utilize information related tothe patient's sleep state. Because disordered breathing occurs morefrequently during sleep, assessment of rhythm-related breathingdisorders may involve determination of whether the patient is asleep.Other types of cardiopulmonary disorders may be modified by thepatient's sleep state. The cardiopulmonary status processor may usesleep state information in connection with the assessment of thepatient's cardiopulmonary status. Methods and systems for sleep and/orsleep stage detection, aspects of which may be utilized in connectionwith a therapy control system described herein, are described incommonly owned U.S. Pat. No. 7,189,204, and U.S. Publication No.2005/0043652, which are incorporated herein by reference.

The cardiopulmonary status processor 130 develops signals related to thepatient's cardiopulmonary status. These signals are transmitted to atherapy controller 140 that utilizes signals to control therapydelivered to the patient. The controlled therapy may comprise arespiratory therapy delivered to the patient by a respiratory therapydelivery system 115, a cardiac therapy delivered to the patient by acardiac therapy delivery system 152, or a therapy delivered by anothertherapy system 160, e.g., internal or external nerve or musclestimulator and/or internal or external drug pump. Various methods andsystems for implementing cardiac therapy to treat disordered breathingare described in commonly owned U.S. Pat. No. 7,720,541, which isincorporated herein by reference.

FIG. 2 illustrates a block diagram of a therapy system including arespiratory therapy device 210, e.g., CPAP device or other respiratorytherapy device, which may be used to provide external respiratorytherapy for disordered breathing. The respiratory therapy device 210includes one or more sensors 235, e.g., flow, pressure and/or exhaledgas concentration sensors used to sense respiratory conditions and/orother conditions useful in the assessment of the patient'scardiopulmonary status. Signals generated by the sensors 235 areprocessed by signal processing circuitry 230 within the respiratorytherapy device 210.

The respiratory therapy device 210 may comprise any of thepatient-external respiratory therapy devices, including CPAP, bi-levelpositive airway pressure (bi-PAP), proportional positive airway pressure(PPAP), and/or autotitration positive airway pressure devices, forexample. It is understood that a portion of a patient-externalrespiratory therapy device 210 may be positioned within an orifice ofthe body, such as the nasal cavity or mouth, yet can be consideredexternal to the patient.

Continuous positive airway pressure (CPAP) devices deliver a set airpressure to the patient. The pressure level for the individual patientmay be determined during a titration study. Such a study may take placein a sleep lab, and involves determination of the optimum airwaypressure by a sleep physician or other professional. The CPAP devicepressure control is set to the determined level. When the patient usesthe CPAP device, a substantially constant airway pressure level ismaintained by the device.

Autotitration PAP devices are similar to CPAP devices, however, thepressure controller for autotitration devices automatically determinesthe air pressure for the patient. Instead of maintaining a constantpressure, the autotitration PAP device evaluates sensor signals and thechanging needs of the patient to deliver a variable positive airwaypressure. Autotitration PAP and CPAP are often used to treat sleepdisordered breathing, for example.

Bi-level positive airway pressure (bi-PAP) devices provide two levels ofpositive airway pressure. A higher pressure is maintained while thepatient inhales. The device switches to a lower pressure duringexpiration. Bi-PAP devices are used to treat a variety of respiratorydysfunctions, including chronic obstructive pulmonary disease (COPD),respiratory insufficiency, and ALS or Lou Gehrig's disease, amongothers.

The respiratory therapy device 210 may include a device that providespositive and negative airflow pressure to the patient. Respiratorytherapy, including sleep disordered breathing therapy, may be providedby a servo ventilation device. Servo ventilation devices provide airwaypressure dependent on the respiration cycle stage. A servo ventilationdevice provides positive pressure on inhalation and negative pressure onexhalation.

The breathing therapy delivery unit 220 includes a flow generator 221that pulls in air through a filter. The flow generator 221 is controlledby the pressure control circuitry 222 to deliver an appropriate airpressure to the patient. Air flows through tubing 223 and is deliveredto the patient's airway through a mask 224. In one example, the mask 224may be a nasal mask covering only the patient's nose. In anotherexample, the mask 224 covers the patient's nose and mouth.

The respiratory therapy device 210 may include a communications unit 240for communicating with a compatible communications unit 241 of one ormore separate devices, such as an implantable device 270. In oneexample, the respiratory therapy device 210 sends information aboutsensed respiratory flow, pressure, and expired gas to the implantabledevice. The respiratory therapy device receives therapy controlinformation controlling the therapy delivered by the respiratory therapydevice 210 from the implantable device 270.

The implantable device 270, which may comprise an implantable cardiacdevice, includes a cardiopulmonary status processor 250 used to assessthe cardiopulmonary status of the patient. The cardiopulmonary statusprocessor 250 uses the sensor information transferred to the implantabledevice 270 from the respiratory therapy device 210 to determine thestatus of the patient's cardiopulmonary system. Information from therespiratory therapy device sensors 235 may be transferred from therespiratory therapy device 210 to the implantable device 270 throughcommunications units 240, 241 of the respective devices 210, 270. Insome embodiments, the cardiopulmonary assessment processor 250 may useinformation acquired by the respiratory therapy device sensors 235 inaddition to other information received from other devices and/or sensorsin performing the cardiopulmonary status assessment.

The implantable device 270 may additionally or alternatively include atherapy controller 260 that develops therapy control signals based onthe patient's assessed cardiopulmonary status. Therapy control signalsdeveloped by the therapy controller 260 may be transmitted to therespiratory therapy device 210 through the communications units 241,240. The therapy control signals are used to control the therapydelivered by the respiratory therapy device. For example, if thecardiopulmonary assessment processor 250 detects a presence of acardiopulmonary disease, the delivery of respiratory therapy to thepatient may be controlled to treat the detected cardiopulmonary diseasepresence. In other examples, delivery of the respiratory therapy may becontrolled to improve patient comfort based on the assessedcardiopulmonary status, or to meet other therapeutic goals.

The therapy controller 260 may control the respiratory therapy byinitiating, terminating or modifying the respiratory therapy.Controlling the respiratory therapy may involve initiating, terminatingor modifying one or more therapy parameters. For example, the therapycontroller 260 may be used to modify gas pressure or gas flow deliveredby the respiratory therapy device 210. The therapy controller 260 mayinitiate or terminate a gas flow or modify a gas concentration of therespiratory therapy, for example.

Additionally or alternatively, the therapy controller 260 may developcontrol signals used to control therapy delivered by the implantabledevice 270. The implantable device therapy may be controlled to treat adetected cardiopulmonary disease or disorder, to improve patientcomfort, or for other purposes. In one embodiment, the implantabledevice comprises a cardiac therapy device that delivers cardiacelectrical stimulation therapy to the patient. The therapy controllerinitiate or terminate the cardiac electrical stimulation therapy and/orcontrol various parameters of the cardiac electrical stimulation, e.g.,stimulation energy, stimulation timing. The cardiac electricalstimulation therapy may involve non-excitatory electrical stimulationinvolving sub-capture threshold stimulation or stimulation during arefractory period, for example. The therapy controller may modify one ormore parameters of the non-excitatory electrical stimulation therapy.

The cardiac electrical stimulation may involve cardiac pacing therapy.The therapy controller may initiate or terminate the pacing therapy. Thetherapy controller may modify the cardiac pacing therapy by alter apacing rate (e.g., change from a normal sleep rate to an overdrivepacing rate), pacing timing (e.g., modify the AV delay or other pacingtiming parameter), pacing mode, (e.g., switch from DDD to VVI pacing orfrom a tracking mode to a non-tracking pacing mode) and/or pacing type(e.g., switch from dual chamber to biventricular pacing or from singlechamber to dual chamber).

FIG. 3 illustrates a system for implementing therapy control based oncardiopulmonary status in accordance with embodiments of the invention.According to the embodiment illustrated in FIG. 3, a medical system 300includes an implantable cardiac rhythm management (CRM) device 310 thatcooperates with a patient-external respiratory therapy device 320 toprovide therapy control based on cardiopulmonary status. The CRM device310 may provide a first set of monitoring, diagnostic or therapeuticfunctions to the patient. The CRM device 310 may be electrically coupledto the patient's heart 340 through electrodes positioned in, on or aboutthe heart. The cardiac electrodes may sense cardiac electrical signalsproduced by the heart and/or may provide therapy in the form ofelectrical stimulation pulses to one or more heart chambers. Forexample, the cardiac electrodes may deliver electrical stimulation toone or more heart chambers and/or to one or multiple sites within theheart chambers. The CRM device 310 may deliver a variety of cardiactherapies, such as cardiac pacing, defibrillation, cardioversion,cardiac resynchronization, and/or other cardiac therapies, for example.In addition, the CRM device 310 may facilitate control of the externalrespiratory device 320.

The CRM device 310 includes a cardiopulmonary assessment processor andtherapy controller 311 disposed within the housing of the CRM device310. The cardiopulmonary assessment processor and therapy controller 311utilizes physiological signals sensed by an external respiratory therapydevice 320 to assess a cardiopulmonary status of the patient and todevelop control signals to control the therapy delivered by therespiratory therapy device 320, the CRM device 310 or both devices 310,320.

In the example illustrated in FIG. 3, the external respiratory therapydevice 320 comprises a continuous positive airway pressure (CPAP)device. The CPAP device develops a positive air pressure that isdelivered to the patient's airway through tubing 352 and mask 354. CPAPdevice are often used to treat disordered breathing. In oneconfiguration, for example, the positive airway pressure provided by theCPAP device 320 acts as a pneumatic splint keeping the patient's airwayopen and reducing the severity and/or number of occurrences ofdisordered breathing due to airway obstruction.

In addition to the therapy described above, the CPAP device 320 mayprovide a number of monitoring, and/or diagnostic functions in relationto the patient's cardiopulmonary system. Physiological signals sensed bythe sensor system of the CPAP device 320 may be used to assess thepatient's cardiopulmonary status. Therapy delivered by the CPAP device320, the CRM device 310, and/or other therapy devices may be controlledbased on the patient's cardiopulmonary status.

In one implementation, the therapy controller 311 may signal one or bothof the respiratory therapy device 320 and the cardiac therapy device 310to initiate, terminate or modify the therapy delivered by the respectivedevices. The therapy controller 311 may be programmed to recognize andrespond to various changes in cardiopulmonary status based on theconditions sensed by the sensing systems of the respiratory therapydevice 320 and/or the cardiac therapy device 310.

For example, the therapy controller 311 may compare the cardiopulmonarystatus of the patient derived from the sensed conditions to acardiopulmonary status criteria stored in the therapy controller 311.The therapy controller 311 may include decision logic that determines iftherapy changes are indicated based on the comparison of the determinedcardiopulmonary status to the cardiopulmonary criteria.

The CRM device 310 and the CPAP device 320 may communicate directlythrough a wireless communication link, for example. Alternatively, oradditionally, the CRM device 310 and the CPAP device 320 may be coupledvia a wireless or wired communications link, for example, to a separatedevice such as a patient information server 330 that is part of anadvanced patient management (APM) system. The APM patient informationserver 330 may be used to facilitate communication between the medicaldevices 310, 320. The APM patient information server 330 may be used,for example, to download and store data collected by the CRM device 310and/or the CPAP device 320.

Data stored on the APM patient management server 330 may be accessibleby the patient and/or the patient's physician through terminals, e.g.,remote terminals located in the patient's home or physician's office.The APM patient information server 330 may be used to communicate to oneor more of the medical devices 310, 320 to facilitate control of themonitoring, diagnostic and/or therapeutic functions of the devices 310,320. Systems and methods involving advanced patient management systems,aspects of which may be incorporated in connection with therapy controlbased on cardiopulmonary status as in accordance with embodimentspresented herein, are described in U.S. Pat. Nos. 6,336,903, 6,312,378,6,270,457, and 6, 398,728 which are incorporated herein by reference.

In one embodiment, the CRM device 310 and the CPAP device 320 do notcommunicate directly, but may communicate indirectly through the APMserver 330. In this embodiment, the APM system 330 operates as anintermediary between two or more medical devices 310, 320. For example,sensor information relevant to the assessment of the patient'scardiopulmonary status may be transferred from the CPAP device 320 tothe APM system 330. The APM system 330 may then transfer the sensorinformation to the CRM device 310 for use in cardiopulmonary statusassessment. The CRM device 310 may transfer respiratory therapy controlinformation from the CRM device 310 to the APM system 330. The APMsystem 330 may then transfer the respiratory therapy control informationto the CPAP device 320.

Although FIG. 3 illustrates a system comprising a CRM device 310 usedwith a CPAP device 320 to provide therapy controlled by the patient'scardiopulmonary status, any number of patient-internal and/orpatient-external devices may be included in the system 300. For example,a drug delivery device, such as a drug pump or controllable nebulizer,may be included in the system 300. The drug delivery device, or otherdevice, may include sensors that sense conditions used to assess thepatient's cardiopulmonary status. The drug delivery device, or otherdevice, may deliver a therapy controlled based on the patient's assessedcardiopulmonary status.

FIG. 4 is a partial view of an implantable device that may includecircuitry for implementing therapy control based on cardiopulmonarystatus in accordance with embodiments of the invention. In this example,the cardiopulmonary status processor 435 the implantable is configuredas a component of a pulse generator 405 of a cardiac rhythm managementdevice (CRM) 400. The cardiopulmonary status processor 435 includes aninterface for receiving signals from a sensor system of apatient-external respiratory therapy device. Additionally, thecardiopulmonary status processor 435 may receive signals from one ormore sensors of the CRM. In some embodiments, a therapy controller maybe additionally configured as a component of the cardiac rhythmmanagement device 400. The cardiopulmonary status processor 435 and/orthe therapy controller may alternatively be implemented in a variety ofimplantable monitoring, diagnostic, and/or therapeutic devices, such asan implantable cardiac monitoring device, an implantable drug deliverydevice, or an implantable neurostimulation device, for example.

The implantable pulse generator 405 is electrically and physicallycoupled to an intracardiac lead system 410. Portions of the intracardiaclead system 410 are inserted into the patient's heart 490. Theintracardiac lead system 410 includes one or more electrodes configuredto sense electrical cardiac activity of the heart, deliver electricalstimulation to the heart, sense the patient's transthoracic impedance,and/or sense other physiological parameters, e.g., cardiac chamberpressure or temperature. Portions of the housing 401 of the pulsegenerator 405 may optionally serve as a can electrode.

Communications circuitry is disposed within the housing 401,facilitating communication between the pulse generator 405 including thecardiopulmonary status processor 435 and another device or system, suchas the sensing system of a respiratory therapy device and/or APM system.The communications circuitry can also facilitate unidirectional orbidirectional communication with one or more implanted, external,cutaneous, or subcutaneous physiologic or non-physiologic sensors,patient-input devices and/or information systems.

The pulse generator 405 may optionally incorporate an activity sensor420. The activity sensor may be configured, for example, to sensepatient activity. Patient activity may be used in connection, forexample, with rate adaptive pacing, and/or sleep detection. The motionsensor 420 may be implemented as an accelerometer positioned in or onthe housing 401 of the pulse generator 405. If the motion sensor 420 isimplemented as an accelerometer, the motion sensor 420 may also provideacoustic information, e.g. rales, coughing, S1-S4 heart sounds, cardiacmurmurs, and other acoustic information.

The lead system 410 of the CRM 400 may incorporate a transthoracicimpedance sensor that may be used to acquire the patient's respirationwaveform, or other respiration-related information. The transthoracicimpedance sensor may include, for example, one or more intracardiacelectrodes 441, 442, 451-455, 463 positioned in one or more chambers ofthe heart 490. The intracardiac electrodes 441, 442, 451-455, 463 may becoupled to impedance drive/sense circuitry 430 positioned within thehousing of the pulse generator 405.

In one implementation, impedance drive/sense circuitry 430 generates acurrent that flows through the tissue between an impedance driveelectrode 451 and a can electrode on the housing 401 of the pulsegenerator 405. The voltage at an impedance sense electrode 452 relativeto the can electrode changes as the patient's transthoracic impedancechanges. The voltage signal developed between the impedance senseelectrode 452 and the can electrode is detected by the impedance sensecircuitry 430. Other locations and/or combinations of impedance senseand drive electrodes are also possible. The impedance signal may also beused to detect other physiological changes besides respiration thatresult in a change in impedance, including pulmonary edema, heart size,cardiac pump function, etc. The respiratory and/or pacemaker therapy maybe altered on the basis of the patient's heart condition as sensed byimpedance.

The voltage signal developed at the impedance sense electrode 452 isproportional to the patient's transthoracic impedance and represents thepatient's respiration waveform. The transthoracic impedance increasesduring respiratory inspiration and decreases during respiratoryexpiration. The transthoracic impedance may be used to determine theamount of air moved in one breath, denoted the tidal volume and/or theamount of air moved per minute, denoted the minute ventilation. A normal“at rest” respiration pattern, e.g., during non-REM sleep, includesregular, rhythmic inspiration—expiration cycles without substantialinterruptions, as indicated in FIG. 7.

Returning to FIG. 4, the lead system 410 may include one or more cardiacpace/sense electrodes 451-455 positioned in, on, or about one or moreheart chambers for sensing electrical signals from the patient's heart490 and/or delivering pacing pulses to the heart 490. The intracardiacsense/pace electrodes 451-455, such as those illustrated in FIG. 4, maybe used to sense and/or pace one or more chambers of the heart,including the left ventricle, the right ventricle, the left atriumand/or the right atrium. The lead system 410 may include one or moredefibrillation electrodes 441, 442 for deliveringdefibrillation/cardioversion shocks to the heart.

The pulse generator 405 may include circuitry for detecting cardiacarrhythmias and/or for controlling pacing or defibrillation therapy inthe form of electrical stimulation pulses or shocks delivered to theheart through the lead system 410. The cardiopulmonary status processor435 may be disposed within the housing 401 of the pulse generator 405.The cardiopulmonary status processor 435 may be coupled to varioussensors, including the transthoracic impedance sensor 430 and activitysensor 420, patient-external respiration therapy device and/or systemsor devices through leads or through wireless communication links.

The cardiopulmonary status processor 435 may be coupled to a therapycontrol unit configured to develop control information for therapydelivered to the patient based on the patient's cardiopulmonary status.In one embodiment, the therapy controller may also be configured as acomponent of the pulse generator 405 and may be positioned within thepulse generator housing 401. In another embodiment, the therapycontroller may be positioned outside the pulse generator housing 401 andcommunicatively coupled to the cardiopulmonary status processor 435,e.g., through a wireless communications link.

FIG. 5 is a diagram illustrating an implantable transthoracic cardiacdevice that may be used in connection with therapy control based oncardiopulmonary status in accordance with embodiments of the invention.The implantable device illustrated in FIG. 5 is an implantabletransthoracic cardiac sensing and/or stimulation (ITCS) device that maybe implanted under the skin in the chest region of a patient. The ITCSdevice may, for example, be implanted subcutaneously such that all orselected elements of the device are positioned on the patient's front,back, side, or other body locations suitable for sensing cardiacactivity and delivering cardiac stimulation therapy. It is understoodthat elements of the ITCS device may be located at several differentbody locations, such as in the chest, abdominal, or subclavian regionwith electrode elements respectively positioned at different regionsnear, around, in, or on the heart.

Circuitry for implementing a cardiopulmonary status processor orcardiopulmonary status processor and a therapy controller may bepositioned within the primary housing of the ITCS device. The primaryhousing (e.g., the active or non-active can) of the ITCS device, forexample, may be configured for positioning outside of the rib cage at anintercostal or subcostal location, within the abdomen, or in the upperchest region (e.g., subclavian location, such as above the third rib).In one implementation, one or more electrodes may be located on theprimary housing and/or at other locations about, but not in directcontact with the heart, great vessel or coronary vasculature.

In another implementation, one or more electrodes may be located indirect contact with the heart, great vessel or coronary vasculature,such as via one or more leads implanted by use of conventionaltransvenous delivery approaches. In another implementation, for example,one or more subcutaneous electrode subsystems or electrode arrays may beused to sense cardiac activity and deliver cardiac stimulation energy inan ITCS device configuration employing an active can or a configurationemploying a non-active can. Electrodes may be situated at anteriorand/or posterior locations relative to the heart.

In the configuration shown in FIG. 5, a subcutaneous electrode assembly507 can be positioned under the skin in the chest region and situateddistal from the housing 502. The subcutaneous and, if applicable,housing electrode(s) can be positioned about the heart at variouslocations and orientations, such as at various anterior and/or posteriorlocations relative to the heart. The subcutaneous electrode assembly 507is coupled to circuitry within the housing 502 via a lead assembly 506.One or more conductors (e.g., coils or cables) are provided within thelead assembly 506 and electrically couple the subcutaneous electrodeassembly 507 with circuitry in the housing 502. One or more sense,sense/pace or defibrillation electrodes can be situated on the elongatedstructure of the electrode support, the housing 502, and/or the distalelectrode assembly (shown as subcutaneous electrode assembly 507 in FIG.5).

It is noted that the electrode and the lead assemblies 507, 506 can beconfigured to assume a variety of shapes. For example, the lead assembly506 can have a wedge, chevron, flattened oval, or a ribbon shape, andthe subcutaneous electrode assembly 507 can comprise a number of spacedelectrodes, such as an array or band of electrodes. Moreover, two ormore subcutaneous electrode assemblies 507 can be mounted to multipleelectrode support assemblies 506 to achieve a desired spacedrelationship amongst subcutaneous electrode assemblies 507.

In particular configurations, the ITCS device may perform functionstraditionally performed by cardiac rhythm management devices, such asproviding various cardiac monitoring, pacing and/orcardioversion/defibrillation functions. Exemplary pacemaker circuitry,structures and functionality, aspects of which can be incorporated in anITCS device of a type that may benefit from multi-parameter sensingconfigurations, are disclosed in commonly owned U.S. Pat. Nos.4,562,841; 5,284,136; 5,376,476; 5,036,849; 5,540,727; 5,836,987;6,044,298; and 6,055,454, which are hereby incorporated herein byreference in their respective entireties. It is understood that ITCSdevice configurations can provide for non-physiologic pacing support inaddition to, or to the exclusion of, bradycardia and/or anti-tachycardiapacing therapies. Exemplary cardiac monitoring circuitry, structures andfunctionality, aspects of which can be incorporated in an ITCS of thepresent invention, are disclosed in commonly owned U.S. Pat. Nos.5,313,953; 5,388,578; and 5,411,031, which are hereby incorporatedherein by reference in their respective entireties.

An ITCS device can incorporate circuitry, structures and functionalityof the subcutaneous implantable medical devices disclosed in commonlyowned U.S. Pat. Nos. 5,203,348; 5,230,337; 5,360,442; 5,366,496;5,397,342; 5,391,200; 5,545,202; 5,603,732; and 5,916,243 and commonlyowned U.S. Patent Application Ser. No. 60/462,272, filed Apr. 11, 2003,Ser. No. 10/462,001, filed Jun. 13, 2003, now U.S. Publication No.2004/0230229, Ser. No. 10/465,520, filed Jun. 19, 2003, now U.S.Publication No. 2004/0230230, Ser. No. 10/820,642 filed Apr. 8, 2004,now U.S. Pat. No. 7,570,997, and Ser. No. 10/821,248, filed Apr. 8,2004, now U.S. Publication No. 2004/0215240, which are incorporatedherein by reference.

The housing of the ITCS device may incorporate components of amonitoring unit 409, including a memory, sensor interface, and/or eventdetector circuitry. The monitoring unit 509 may be coupled to one ormore sensors, patient input devices, and/or information systems. In someembodiments, the housing of the ITCS device may also incorporatecomponents of a therapy feedback unit. In other embodiments, circuitryto implement the therapy feedback unit may be configured within a deviceseparate from the ITCS device. In this embodiment, the therapy feedbackunit and the monitoring unit may be communicatively coupled using leadsor a wireless communication link, for example.

In one implementation, the ITCS device may include an impedance sensorconfigured to sense the patient's transthoracic impedance. The impedancesensor may include the impedance drive/sense circuitry incorporated withthe housing 502 of the ITCS device and coupled to impedance electrodespositioned on the can or at other locations of the ITCS device, such ason the subcutaneous electrode assembly 507 and/or lead assembly 506. Inone configuration, the impedance drive circuitry generates a currentthat flows between a subcutaneous impedance drive electrode and a canelectrode on the primary housing of the ITCS device. The voltage at asubcutaneous impedance sense electrode relative to the can electrodechanges as the patient's transthoracic impedance changes. The voltagesignal developed between the impedance sense electrode and the canelectrode is sensed by the impedance drive/sense circuitry.

Communications circuitry is disposed within the housing 502 forfacilitating communication between the ITCS device, including thecardiopulmonary status processor 509, and an external communicationdevice, such as a portable or bed-side communication station,patient-carried/worn communication station, or external programmer, forexample. The communications circuitry facilitates communication ofsignals developed by a sensing system of a patient-external respiratorytherapy device and used by the cardiopulmonary status processor inconnection with assessment of the patient's cardiopulmonary status. Thecommunications circuitry can also facilitate unidirectional orbidirectional communication with one or more external, cutaneous, orsubcutaneous physiologic or non-physiologic sensors.

Assessment of cardiopulmonary status may include assessing the patient'spulmonary function as previously described. In some implementations, thecardiopulmonary status processor may use sensed conditions acquired bythe respiratory therapy device, and/or other therapy or diagnosticdevices to assess patient's cardiopulmonary status. Cardiopulmonarystatus assessment may comprise evaluating a presence of cardiac and/orpulmonary disease. The charts provided in FIGS. 6A-6N illustrateconditions and sensors that may be used to determine physiologicalchanges associated with various cardiac and/or pulmonary diseases anddisorders.

The left section 602 of FIG. 6A illustrates various conditions that maybe sensed using sensors of a respiratory therapy device (CPAP), acardiac device (CRM), or an external non-CPAP, non-CRM device. The topsection 601 lists various conditions that may be sensed and providesinformation about sensors used to sense the conditions. The centersection 604 of FIG. 6A provides physiological changes and/or symptomsthat may be evaluated using the conditions listed in the left section602. The right section 603 of FIG. 6A provides pulmonarydiseases/disorders. The presence of the pulmonary diseases/disorders ofthe right section 603 may be assessed based on the physiological changesand/or symptoms of the center section 604.

For legibility, the left and right sections 602, 603 of FIG. 6A aredivided into sixteen portions, FIGS. 6B-1-6G-2. FIGS. 6B-1-6B-4represent the upper left portions 610-1 to 610-4 of the left section 602of FIG. 6A. FIGS. 6C-1-6C-2 represent the upper right portions 612-1 to612-2 of the left section 602 of FIG. 6A. FIGS. 6D-1-6D-4 represent thelower left portions 614-1 to 614-4 of the left section 602 of FIG. 6A.FIGS. 6E-1-6E-2 represent the lower right portions 616-1 to 616-2 of theleft section 602 of FIG. 6A. FIGS. 6F-1-6F-2 represent the upperportions 620-1 to 620-2 of the right section 604 of FIG. 6A. FIGS.6G-1-6G-2 represent the lower portions 622-1 to 622-2 of the rightsection 604 of FIG. 6A. Relevant portions of the center section 604 andthe top section 601 of FIG. 6A appear in each of the FIGS. 6B-1-6G-2 forconvenience.

The charts provided in FIGS. 6H-6N illustrate conditions and sensorsthat may be used to determine physiological changes associated withvarious cardiac diseases and disorders. The left section 632 of FIG. 6Hillustrates various conditions that may be sensed using sensors of arespiratory therapy device (CPAP), a cardiac device (CRM), or anexternal non-CPAP, non-CRM device. The center section 634 of FIG. 6Hprovides physiological changes and/or symptoms that may be evaluatedusing the conditions listed in the left section 632. The right section636 of FIG. 6H lists cardiac diseases/disorders. The presence of thecardiac diseases/disorders of the right section 636 may be assessedbased on the physiological changes and/or symptoms of the center section634.

For legibility, the chart of FIG. 6H is divided into ten portions, FIGS.6I-1-6N. FIGS. 6I-1-6I-2 represent the upper left portion 640 portions640-1 to 640-2 of the left section 632 of FIG. 6H. FIGS. 6J-1-6J-2represent the upper right portions 642-1 to 642-2 of the left section632 of FIG. 6H. FIGS. 6K-1-6K-2 represent the lower left portions 644-1to 644-2 of the left section 632 of FIG. 6H. FIGS. 6L-1-6L-2 representthe lower right portions 646-1 to 646-2 of the left section 632 of FIG.6H. FIG. 6M represents the upper portion 650 of the right section 636 ofFIG. 6H. FIG. 6N represents the lower portion 652 of the right section636 of FIG. 6H. Relevant portions of the center section 604 and the topsection 601 of FIG. 6H appear in each of the FIGS. 6I-1-6N forconvenience.

An example of how FIGS. 6A-6N may be used follows. Referring to FIGS.6F-1 to 6G-2, the restrictive pulmonary disorder pneumoconiosis producesthe physiological changes non-specific dyspnea (FIG. 6 F-1) and cough(FIG. 6G-1). Non-specific dyspnea (FIG. 6 F-1) and cough (FIG. 6G-1) areindicated by X or D marks in the column denoted pneumoconiosis in FIGS.6F-1 and 6G-2, respectively. An “X” mark indicates that the symptom orphysiological change may be derived from the sensed condition. A “D”mark indicates that the symptom or physiological change may be directlydetermined from the sensed condition. Non-specific dyspnea may bedetected based on one or more of the conditions listed in the row fornon-specific dyspnea illustrated in FIGS. 6B-1, 6B-3, and 6C-1. Theconditions include duration of symptoms, abnormal breathing/coughing,blood pO2, inspiratory flow, expiratory flow, exhaled % CO2 and exhaled% O2, illustrated in FIG. 6C-1. The conditions also includearterial/venous pO2, blood pCO2, blood pO2, exhalation time, inspirationtime, minute ventilation, tidal volume, respiration rate, FIG. 6B-3,and/or respiration sounds illustrated in FIG. 6B-1.

The presence of a disorder/disease, such as those listed in FIGS. 6A-6N,may be assessed by based on physiological changes and/or symptomsassociated with the disorder/disease. The physiological changes and/orsymptoms may be detected using conditions sensed by a sensor system of arespiratory therapy alone or in combination with the sensor systems ofother therapeutic or diagnostic medical devices. If the sensedconditions indicate that the physiological changes or symptoms of adisease or disorder are consistent with a threshold level, the presenceof the disease or disorder may be determined.

In another example, assessment of disease presence may be based onrelative changes in one or more conditions indicative of physiologicalchanges or symptoms caused by the disease. For example, assessment of apresence of a disease or disorder may be accomplished by evaluating thechanges in conditions indicative of physiological changes or symptomscaused by the disease. The changes in the one or more conditions may becompared to threshold criteria. If changes in the conditions indicativeof physiological changes or symptoms caused by the disease areconsistent with threshold levels, a presence of the disease or disordermay be determined.

In a further example, the threshold criteria may involve relationshipsbetween the conditions indicative of physiological changes or symptomscaused by the disease. The presence of a disease may be assessed byevaluating relationships between conditions indicative of physiologicalchanges or symptoms caused by the disease. For example, assessment of adisease may involve the determination that levels or amounts of two ormore conditions have a certain relationship with one another. Ifrelationships between the conditions indicative of physiological changesor symptoms caused by the disease are consistent with thresholdrelationship criteria, the disease or disorder may be present.

Techniques for assessing a presence of various pulmonary diseases,aspects of which may be incorporated into the embodiments describedherein, are discussed in commonly owned U.S. Pat. No. 7,575,553,incorporated herein by reference.

FIG. 7 is a flowchart illustrating a method in accordance withembodiments of the invention. One or more threshold criteria sets forassessment of cardiopulmonary status based on the disease/disorderpresence are established 710. A respiratory therapy device such as aCPAP device may be used to sense 712 conditions modulated by diseasesymptoms. The sensor information may be collected periodically, e.g.,nightly, and stored for evaluation. If a presence of the disease has notbeen previously determined 715, then the levels of the sensed conditionsare compared 720 to a set of criteria associated with the disease. Iflevels of the conditions are consistent 725 with the threshold criterialevels, then a presence of the disease is determined 730. Therapy may bemodified based on the presence of the disease/disorder. In oneimplementation, therapy may be initiated 735 to treat the disease.

If levels of the conditions are not consistent 725 with the thresholdcriteria levels, then the system continues to sense conditions modulatedby disease symptoms and collect 712 data based on the sensed conditions.

If the presence of the disease was previously determined 715, then theprogression of the disease may be monitored 740 based on the conditionsand/or criteria used to determine a presence of the disease, or usingother conditions and/or criteria. If the disease presence is stilldetected 745 based on the conditions and criteria used for monitoring,then therapy may be maintained or modified 750 based on the diseaseprogression. Disease progression may be determined, for example, bytrending one or more conditions used for monitoring the disease presenceover a period of time. Modifications to the therapy may be made based onthe condition trends. When the disease presence is no longer detected745, the therapy may be terminated 755.

A number of the examples presented herein involve block diagramsillustrating functional blocks used for monitoring functions inaccordance with embodiments of the present invention. It will beunderstood by those skilled in the art that there exist many possibleconfigurations in which these functional blocks can be arranged andimplemented. The examples depicted herein provide examples of possiblefunctional arrangements used to implement the approaches of theinvention.

The components and functionality depicted as separate or discreteblocks/elements in the figures in general can be implemented incombination with other components and functionality. The depiction ofsuch components and functionality in individual or integral form is forpurposes of clarity of explanation, and not of limitation. It is alsounderstood that the components and functionality depicted in the Figuresand described herein can be implemented in hardware, software, or acombination of hardware and software.

1. A method, comprising: sensing a first set of one or morephysiological parameters using one or more first sensors of a firstmedical unit configured to operate outside a patient's body; sensing asecond set of one or more physiological parameters using one or moresecond sensors of a second medical unit configured for operation insidethe patient's body; identifying, based on one or both of the first setof physiological parameters and the second set of physiologicalparameters, a cardiopulmonary disorder affecting a patient as abreathing rhythm disorder or identifying, based on one or both of thefirst set of physiological parameters and the second set ofphysiological parameters, the cardiopulmonary disorder affecting thepatient as a non-rhythm breathing disorder, wherein identifying thecardiopulmonary disorder as a non-rhythm breathing disorder comprisesdiscriminating between chronic bronchitis, asthma, emphysema, pulmonaryedema and at least one other pulmonary vascular disorder; andcontrolling a therapy delivered to the patient based on the identifiedcardiopulmonary disorder, wherein at least one of identifying andcontrolling are performed using circuitry.
 2. The method of claim 1,wherein the at least one other pulmonary vascular disorder comprisespulmonary hypertension.
 3. The method of claim 1, wherein identifyingthe non-rhythm breathing disorder comprises identifying an obstructivepulmonary disease or a restrictive pulmonary disease.
 4. The method ofclaim 1, wherein identifying the non-rhythm breathing disorder comprisesidentifying an infectious pulmonary disease or a non-infectiouspulmonary disease.
 5. The method of claim 1, wherein identifying thebreathing rhythm disorder comprises discriminating between apnea and atleast one other breathing rhythm disorder.
 6. The method of claim 5,wherein the at least one other breathing rhythm disorder comprises oneor more of hypopnea, Cheyne-Stokes respiration, and periodic breathing.7. The method of claim 1, wherein identifying the cardiopulmonarydisorder comprises learning to recognize a presence of thecardiopulmonary disorder based on a history of the physiologicalparameters.
 8. The method of claim 1, wherein identifying the non-rhythmbreathing disorder includes identifying a pleural disorder.
 9. Themethod of claim 8, wherein identifying the pleural disorder comprisesdiscriminating between pleural effusion, pneumothorax, and hemothorax.10. The method of claim 1, wherein controlling the therapy comprisescontrolling the first medical unit to deliver the therapy.
 11. Themethod of claim 1, wherein controlling the therapy comprises controllingthe second medical unit to deliver the therapy.
 12. A medical system,comprising: one or more first sensors of a first medical unit, the firstmedical unit configured for operation outside a patient's body, the oneor more first sensors configured to sense a first set of one or morephysiological parameters; one or more second sensors of a second medicalunit configured for operation inside a patient's body, the one or moresecond sensors configured to sense a second set of one or morephysiological parameters; a cardiopulmonary status processor configuredto identify, based on one or both of the first set of physiologicalparameters and the second set of physiological parameters, acardiopulmonary disorder affecting a patient as a breathing rhythmdisorder, identify, based on one or both of the first set ofphysiological parameters and the second set of physiological parameters,a cardiopulmonary disorder affecting the patient as a non-rhythmbreathing disorder, wherein the cardiopulmonary status processor isconfigured to discriminate between chronic bronchitis, asthma,emphysema, pulmonary edema and at least one other pulmonary vasculardisorder to identify the non-rhythm breathing disorder; and a therapycontroller configured to control a therapy delivered to the patientbased on the identified cardiopulmonary disorder.
 13. The medical systemof claim 12, wherein the first medical unit comprises an externalrespiratory therapy device.
 14. The medical system of claim 12, whereinthe second medical unit comprises an implantable monitoring device. 15.The medical system of claim 12, wherein the second medical unitcomprises an implantable therapy device.
 16. The medical system of claim12, wherein the cardiopulmonary status processor is configured to learnto recognize a presence of the cardiopulmonary disorder based on ahistory of the physiological parameters.
 17. The medical system of claim12, wherein the cardiopulmonary status processor is configured toidentify the cardiopulmonary disorder as a pleural disorder.
 18. Themedical system of claim 17, wherein the cardiopulmonary status processoris configured to discriminate between pleural effusion, pneumothorax,and hemothorax to identify the pleural disorder.